The introduction of new DNA sequencing technologies presents an exceptional opportunity for creative applications with potential for breakthrough discoveries. Funding is requested for an Illumina Genome Analyzer II (GAII, also called an Illumina Solexa). The instrument will be located in the Cornell University Life Sciences Core Laboratories Center (CLC). The instrument system will be operated with a multidisciplinary, multi-core approach, including support from the DNA sequencing, genotyping, microarrays, information technology and informatics core resources of the Center. Implementation of the Illumina Solexa in a core facility center as a shared resource will enable cost effective access to this vital new technology. The CLC has significant experience in running the requested instrument system. The CLC has had an Illumina Solexa since July 2007 and currently offers this platform as a standard core facility service. This instrument was purchased with non-NIH funding sources. There is a significant backlog on this instrument and projected throughput demand exceeds the capacity of the instrument. To meet demand, a second Illumina Solexa unit has been in the CLC since December 2007, on loan at no cost for six months. Due to the projected high level of use for NIH funded projects, NIH funding is requested for purchase of a second Illumina Solexa instrument. There is a clear need for a second Illumina Solexa instrument to be permanently placed at Cornell as a shared resource. This application describes 19 projects from 21 NIH funded investigator groups that will utilize the instrument. The Illumina Solexa will be used for whole genome assembly, resequencing of PCR amplicons, mutation detection (including sequencing large sets of patient samples to identify mutations in disease candidate genes), SNP genotyping, genome-wide measurements of protein-nucleic interactions, and small RNA profiling for gene expression and gene regulation studies. The Illumina Solexa makes possible experiments that are impractical or impossible with conventional sequencing instruments. The requested instrument will enable NIH funded investigators at Cornell to undertake research projects that would not otherwise be possible. The instrument will facilitate a broad range of current and future NIH funded projects. PUBLIC HEALTH RELEVANCE: The requested Illumina Solexa instrument will play a crucial role in advancing knowledge and understanding in a wide variety of health related research, including studies of cancer transformation (hematologic, ovarian, prostate and mammary malignancies), insulin signaling, immune response, pulmonary disease, neural tube defects, stem cell potential, infertility, neuropsychiatric disease, malaria resistance, and pathogenic bacteria (M. tuberculosis, Streptococcus, and Listeria).